The major objective of this project is to characterize the pulmonary inactivation of catecholamines (especially norepinephrine). Two basic types of experiments (norepinephrine metabolism and norepinephrine uptake) will be performed on three different tissue preparations: 1) isolated perfused rat lung, 2) isolated rat pulmonary artery and vein, and 3) endothelial and smooth muscle cells from these vessels grown in tissue culture. The metabolism of 3H-1-norepinephrine (NE) will be examined in the isolated perfused lung during NE infusion. The effects of monoamine oxidase (MAO) and catechol-0-methyl transferase (COMT) inhibitors alone and in combination will be examined. Isolated perfused rat lungs will be pretreated with MAO and COMT inhibitors to block NE metabolism and then infused with NE to load the tissue. A compartmental analysis will then be performed on the efflux of NE from these lungs to determine the size and efflux rate constant of the various compartments involved in the uptake of NE. The effect of several drugs on the uptake and efflux of NE will be examined. Similar experiments will be performed on portions of pulmonary artery and vein in vitro and on isolated endothelial and smooth muscle cells grown in tissue culture from the pulmonary artery and vein of the rat. These tissues and isolated cells will be incubated with NE to study the metabolism of NE and will be pretreated with MAO and COMT inhibitors and then incubated with NE to study the uptake and efflux of NE. These experiments will be conducted in normotensive and hypertensive rats. Two genetically inbred strains of hypertensive rats will be used: 1) the spontaneously hypertensive rats developed by Okamoto and coworkers and 2) the salt-sensitive and salt-resistant rats developed by Dahl and coworkers. All of these experiments should provide additional information on the mechanisms and site of pulmonary inactivation of NE and the role of these processes in the development of some experimental forms of hypertension.